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Wnt/β-连环蛋白信号通路对流感病毒复制的调控

Regulation of influenza virus replication by Wnt/β-catenin signaling.

作者信息

More Sunil, Yang Xiaoyun, Zhu Zhengyu, Bamunuarachchi Gayan, Guo Yujie, Huang Chaoqun, Bailey Keith, Metcalf Jordan P, Liu Lin

机构信息

The Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.

Oklahoma Center for Respiratory and Infectious Diseases, Stillwater, Oklahoma, United States of America.

出版信息

PLoS One. 2018 Jan 11;13(1):e0191010. doi: 10.1371/journal.pone.0191010. eCollection 2018.

DOI:10.1371/journal.pone.0191010
PMID:29324866
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5764324/
Abstract

Wnt/β-catenin signaling is an essential pathway in cell cycle control. Dysregulation of the Wnt/β-catenin signaling pathway during viral infection has been reported. In this study, we examined the effect of modulating Wnt/β-catenin signaling during influenza virus infection. The activation of the Wnt/β-catenin pathway by Wnt3a increased influenza virus mRNA and virus production in in vitro in mouse lung epithelial E10 cells and mRNA expresson of influenza virus genes in vivo in the lungs of mice infected with influenza virus A/Puerto Rico/8/34. However, the inhibition of Wnt/β-catenin signaling by iCRT14 reduced virus titer and viral gene expression in human lung epithelial A549 cells and viral replication in primary mouse alveolar epithelial cells infected with different influenza virus strains. Knockdown of β-catenin also reduced viral protein expression and virus production. iCRT14 acts at the early stage of virus replication. Treatment with iCRT14 inhibited the expression of the viral genes (vRNA, cRNA and mRNA) evaluated in this study. The intraperitoneal administration of iCRT14 reduced viral load, improved clinical signs, and partially protected mice from influenza virus infection.

摘要

Wnt/β-连环蛋白信号通路是细胞周期调控中的一条重要途径。已有报道称病毒感染期间Wnt/β-连环蛋白信号通路会失调。在本研究中，我们检测了在流感病毒感染期间调节Wnt/β-连环蛋白信号通路的作用。Wnt3a激活Wnt/β-连环蛋白通路会增加体外培养的小鼠肺上皮E10细胞中的流感病毒mRNA和病毒产量，以及感染甲型流感病毒/波多黎各/8/34的小鼠肺内流感病毒基因的体内mRNA表达。然而，iCRT14抑制Wnt/β-连环蛋白信号通路会降低人肺上皮A549细胞中的病毒滴度和病毒基因表达，以及感染不同流感病毒株的原代小鼠肺泡上皮细胞中的病毒复制。敲低β-连环蛋白也会降低病毒蛋白表达和病毒产量。iCRT14作用于病毒复制的早期阶段。用iCRT14处理可抑制本研究中评估的病毒基因（vRNA、cRNA和mRNA）的表达。腹腔注射iCRT14可降低病毒载量，改善临床症状，并部分保护小鼠免受流感病毒感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69c/5764324/096a545fbe83/pone.0191010.g008.jpg
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